The objectives of this research program are to understand the structural and functional aspects of macromolecules at crucial interfaces in biochemistry. Efforts are divided into three principal areas: 1) DNA-protein interactions; substructures of eukaryotic chromosomes and histone-DNA interaction. Principal objective is to determine the number of, and sequence specificity if any, for binding DNA duplex by histone proteins. Phage T7 has been studied by solution diffraction and packaging intermediate structures are under investigation as a means of understanding protein-DNA interactions in a simpler system. 2) The neurochemical acetylcholine receptor from electric fish is the subject of attempts to crystallize purified protein, and to study structure in the membrane. A single crystal study of alpha-Bungarotoxin is in progress at 2.7 A resolution. 3) The high resolution structure analysis of trypsinoaen has been recently completed, and should lead to new proposals for zymogen activation. Infrared spectroscopy has been used to define the pKa's of Asp 102 and Asp 194 at the active center of serine proteases, and study of these pKa's in transition state analogues and in the acyl enzyme should lead to new data on the mechanisms of protease hydrolysis.